Diabetes is a major health concern, as evidenced by the number of people it affects as well as the costs incurred in treating or preventing it. According to the American Diabetes Association, there are 15.7 million people, or 5.9% of the U.S. population, that suffer from diabetes. Only about 10.3 million of these people have been diagnosed with the disease. With approximately 5.4 million people unaware that they have this chronic condition, diabetes ranks as the seventh leading cause of death in the U.S. The costs associated with efforts to treat and/or to prevent the condition are commensurate with the number of people afflicted, both in the U.S. and throughout the world.
Diabetes is a complex condition or disease that is most commonly defined by elevated concentrations of blood glucose, with the disorder affecting the metabolism of carbohydrates, fats and proteins. The disorder results from an inability to control blood glucose levels, for example due to insufficient levels or activity of insulin. Elevated glucose levels, in turn, often lead to secondary health problems that require additional medical treatment. Some of the leading diabetes-related health risks include hyperglycemia, arteriosclerosis, diabetic retinopathy (possibly leading to blindness), cataracts, nephropathy, increased risk of infections, hypertension, nerve disease, risk of amputations, impotence, diabetic ketoacidosis, and dementia. While these health risks are associated with diabetes, they are not, by themselves, useful indicators of diabetes. For example, hypertension may occur with or without diabetes (e.g., due to a genetic predisposition or a high-salt diet).
There are two primary types of diabetes, with many variations of each. Type 1 diabetes generally occurs in childhood and results from the body's inability to produce insulin. Type 2 diabetes is the more prevalent form and results from either insulin deficiency or, more commonly, from insulin resistance. Some diabetics are able to maintain healthy blood glucose concentrations with restrictive diets alone, but most require the assistance of oral hypoglycemic drugs and/or insulin replacement therapy by injection. Drug therapy, however, does not always achieve satisfactory glycemic control and insulin use often promotes hypoglycemia. Moreover, these conventional treatments often lower blood glucose by promoting the non-selective uptake of glucose by many cells, including adipocytes, which contributes to undesirable weight gain. Therefore, continuous treatment modifications and monitoring are often necessary. Additionally, traditional treatments, like insulin injections, are expensive and can be painful to administer.
In addition to conventional treatments relying on insulin injections or over-the-counter medications, natural products, including plant materials, have been reportedly tried in alternative treatments of conditions such as diabetes. This is perhaps unsurprising, given the great variety of plants in the world. As traditional medicines, plants have been used for a variety of real or imagined ailments, with the same plants frequently being used to “treat” unrelated conditions. One of the many plant families used in traditional herbal remedies is the Artemisia family, with over 400 different species.
One species of Artemisia, Artemisia dracunculus, Yazdanparast et al., Biomedical Letters 59:137-141 (1999) has been reported to yield alcohol-based extracts that exhibit an antihyperlipidemic effect on rats fed high-fat diets. The authors of this study did not, however, test for the presence of mutagens or toxins and did not explore the use of such extracts to treat disorders, diseases or conditions other than hyperlipidemia. A. dracunculus and another Artemisia species, Artemisia herba-alba, have been reportedly used to treat headaches and dizziness, e.g., in Middle Eastern cultures. [Al-Waili et al., Clinical and Experimental Pharmacology and Physiology 13:569-573 (1986)]. Additionally, Swanston-Flatt et al., Proc. Nutr. Soc. 50: 641-651 (1991) disclosed the use of tarragon mixtures in treating diabetes, referencing Swanston-Flatt et al., Acta Diabetol. Lat. 26:51-55 (1989), for an explanation that treatments were prepared by mixing homogenized plant material into standard diets. Extracts were never prepared from the tarragon. Swanston-Flatt et al. (1991) reported that tarragon, while reportedly shown to reduce body weight, polydipsia and hyperphagia, did not significantly lower blood glucose concentrations.
Along with the reported medicinal effects of the Artemisia spp, however, is the observation that crude extracts prepared from Artemisia spp have a positive mutagenic effect when tested in a conventional Ames mutagenicity test. PCT Publication WO 97/35598 describes aqueous (i.e., water) extracts of Artemisia judaica as having an insulinomimetic anti-diabetic effect, but also notes the presence of a deleterious mutagen that would render the crude extract unsuitable for administration to mammals such as humans. WO 97/35598 reported that two different preparations from Artemisia judaica tested positive in the Ames test for mutagenicity. Therefore, not all Artemisia plants, e.g., not A. judaica, appear suitable for use in extracts for treating mammals having a disorder such as diabetes.
Thus, there remains a need in the art to develop methods of alleviating, preventing or treating symptoms of diabetes, or the disorder itself, and the health risks associated with diabetes, preferably methods based on the use of readily available and inexpensively produced natural materials such as plants or plant parts. The methods should be both effective and inexpensive without introducing unwarranted toxicity and/or mutagenicity risks. There is also a need to develop methods that modulate enzymes involved in glucose metabolism to facilitate the control of diabetic and non-diabetic symptoms involved in a variety of disorders and diseases found in mammals. There further remains a need to develop an effective method of extracting materials useful for treating diabetes or symptoms of diabetes from a plant or portions of a plant. Additionally, there is a need in the art for methods of controlling body weight, for example in conjunction with diabetes therapies. It is also apparent that for diabetics, athletes, and others, there is a need for increasing the energy store available to a cell, e.g., a muscle cell or neuron.